PITPNC1 Suppress CD8+ T cell immune function and promote radioresistance in rectal cancer by modulating FASN/CD155

作者：Junxian Liang, Limin Liao, Lang Xie, WenWen Tang, Xiang Yu, Yinghao Lu, Hongzhen Chen, Juanli Xu, Lei Sun, Huanmei Wu, Chunhui Cui, Yujing Tan · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-04931-3 · 被引用次数：19 · 研究领域：Immune Cell Function and Interaction、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

Abstract Background Radioresistance is a primary factor contributing to the failure of rectal cancer treatment. Immune suppression plays a significant role in the development of radioresistance. We have investigated the potential role of phosphatidylinositol transfer protein cytoplasmic 1 (PITPNC1) in regulating immune suppression associated with radioresistance. Methods To elucidate the mechanisms by which PITPNC1 influences radioresistance, we established HT29, SW480, and MC38 radioresistant cell lines. The relationship between radioresistance and changes in the proportion of immune cells was verified through subcutaneous tumor models and flow cytometry. Changes in the expression levels of PITPNC1, FASN, and CD155 were determined using immunohistochemistry and western blotting techniques. The interplay between these proteins was investigated using immunofluorescence co-localization and immunoprecipitation assays. Additionally, siRNA and lentivirus-mediated gene knockdown or overexpression, as well as co-culture of tumor cells with PBMCs or CD8 + T cells and establishment of stable transgenic cell lines in vivo, were employed to validate the impact of the PITPNC1/FASN/CD155 pathway on CD8 + T cell immune function. Results Under irradiation, the apoptosis rate and expression of apoptosis-related proteins in radioresistant colorectal cancer cell lines were significantly decreased, while the cell proliferation rate increased. In radioresistant tumor-bearing mice, the proportion...